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Immunocytochemical comparison of cultured normal epithelial prostatic cells with prostatic tissue sections.

By analyzing a culture system of human prostatic epithelial cells (HPEC) and human prostatic fibroblasts (HPF) for expression of several determinants by immunocytochemistry, we have shown that long-term cultures are able to preserve the phenotypic characteristics of the normal tissue from which they are derived. The cytoskeletal elements, prostate-specific proteins, and steroid receptor profiles were compared to those of prostatic epithelium and stroma in situ. When cultured in low serum and low calcium medium, the adult HPEC grew as two layers of cells, the upper one of which retained the differentiation characteristics observed in the luminal fraction of normal prostatic epithelium. This cell type is the likely origin of prostatic neoplasia, with expression of CK8, 18, and 19 but not CK14. Androgen receptors, prostatic-specific antigen, and prostatic acid phosphatase are also expressed in vitro but at lower level than in situ. The lower cell layer expressed most of the same determinants but at a much lower level, suggestive of a stem-cell type. The HPF cultured in RPMI serum supplemented media retained the stromal pattern of the cells observed in situ. Culture systems which conserve the characteristics of their normal counterparts in vivo should provide useful models for studying in vitro genetic and epigenetic factors associated with differentiation and proliferation, but also with tumorigenic progression in the prostatic gland.

Biomarkers↗

Comparison of health-related quality of life and prostate-associated symptoms after primary and salvage cryotherapy for prostate cancer.

PURPOSE: Recent advances in cryosurgery of the prostate have led to the ability to treat tumors successfully with decreased morbidity. The patients' perspectives of this relatively new technique, however, have not yet been addressed. The purpose of this study was to compare health related quality of life (QoL) as well as prostate-associated symptoms in patients after primary and salvage cryoablation for clinically localized prostate cancer using a self-administered questionnaire. METHODS: A total of 131 consecutive patients who underwent cryoablation of the prostate between 1997 and 2001 were included in this confidential mailing study. The patients were either (a) patients with localized prostate cancer with contraindications for radical surgery, including patients refusing other forms of therapy, or (b) had locally recurrent prostate cancer after failure of radiation therapy. All patients received 3 months of neoadjuvant androgen deprivation therapy prior to cryosurgery and were surgically treated by the same surgeon using an argon-based system. We used the EORTC QLQ-C30, a commonly used, multidimensional instrument together with a supplementing, prostate-cancer-specific module. RESULTS: Eighty-one of the 131 patients (response rate 62%) returned the questionnaires. The two groups were comparable regarding age (mean age 72.8 vs 70.1 for the primary and the salvage group, respectively; p=0.22). The overall QoL scores were high in both groups. Primary cryotherapy patients fared significantly better regarding physical (p=0.005) and social (p=0.024) functioning compared with salvage cryotherapy patients. The most prominent prostate-related symptom in both patient groups was sexual dysfunction, followed by urinary symptoms, which were significantly more severe in the salvage group (p=0.001). Incontinence rates were 5.9 and 10% in the primary and the salvage group, respectively. Severe erectile dysfunction was reported in 86 and 90% of the primary and the salvage group, respectively. CONCLUSIONS: The present study demonstrates that, in selected patients, cryotherapy is a treatment option which has a functional outcome comparable to traditionally used prostate cancer treatments. More information regarding QoL is necessary for appropriate patient counseling and individual decision-making in the presence of various treatment alternatives.

Aged↗

Correlation between the total volume, transitional zone volume of the prostate, transitional prostate zone index and lower urinary tract symptoms (LUTS).

OBJECTIVES: Currently available studies show controversial data between the symptoms of the lower urinary tract and the volume of the prostate gland. The objective of the present study is to evaluate the relationship between the score of the lower urinary tract symptoms assessed according to the International Prostate Symptoms Score (IPSS) and the total (TV) and transitional (TZV) zone volume of the prostate and transitional prostate zone index (TZI). MATERIALS AND METHODS: From 223 men with a mean age of 59.3 years (varying from 50 to 75), the scores of lower urinary tract symptoms, measured by the IPSS and TV and TZV, determined by transrectal ultrasonographies, were obtained. Furthermore, the TZI was determined in all cases by the TZV to TV rate of the prostate. The relationship between TV, TZV, and TZI and the data obtained using the symptoms score was statistically determined. RESULTS: The TV of the prostate were 25.5 +/- 10.3, 25.0 +/- 9.3, and 28.9 +/- 13.5 g in individuals with mild, moderate, and severe symptoms, respectively (P = 0.15). Similarly, there was no significant difference when the TZV (7.6 +/- 6.3, 7.6 +/- 5.8, and 9.6 +/- 6.8 g, respectively; P = 0.22) and the TZI (0.26 +/- 0.1, 0.27 +/- 0.1, and 0.30 +/- 0.1, respectively; P = 0.33) were compared in the groups of men with mild, moderate, and severe symptoms of urinary difficulty. However, the quality of life (QoL) scores presented progressively worse values (1.7 +/- 1.3, 3.1 +/- 1.4, and 4.4 +/- 1.2) as the severity of the lower urinary tract symptoms became worse (P < 0.001). The Pearson correlation coefficient between the TV (r = 0.15; P = 0.02), TZV (r = 0.16; P = 0.02), and the TZI (r = 0.14; P = 0.03) with the prostate symptom scores showed low values although they were positive and statistically significant. The highest correlation was observed when the QoL related to urinary symptoms and symptom scores (r = 0.61; P < 0.001) was analyzed. CONCLUSIONS: A low correlation was found between the score lower urinary tract symptoms assessed by IPSS and the different volumes of the prostate gland (TV, TZV) and prostate TZI, and, on the other hand, an inverse correlation between the intensity of urinary symptoms and QoL, supporting the idea of multifactorial aspects related to the genesis of urinary symptoms in men.

Aged↗

Serum levels of vascular endothelial growth factor in patients undergoing prostate biopsy for suspicion of prostate cancer.

OBJECTIVES: To analyze the correlation between serum levels of vascular endothelial growth factor (VEGF) and biopsy findings in patients with a suspicion of prostate cancer. METHODS: Serum levels of VEGF were measured on frozen, archival serum obtained before prostate biopsy in 47 patients with clinical and/or biologic suspicion of prostate cancer. VEGF-A levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The prostate biopsies showed cancer in 27 patients (group 1) and benign tissue in the remaining 20 patients (group 2). No statistically significant difference was found between the two groups in age, digital rectal examination findings, total prostate-specific antigen (PSA) levels, free PSA levels, and complexed PSA levels. The mean prostate volume was significantly lower in group 1 (45.5 g versus 53.9 g; P = 0.04), and the mean percentage of free PSA (free PSA/total PSA) was significantly lower in group 1 (11.3% versus 19%; P = 0.0003). Serum VEGF-A levels were not significantly different between the two groups. The mean VEGF level was 90.6 pg/mL in group 1 and 107.9 pg/mL in group 2 (P = 0.55). Multivariate analysis showed that VEGF-A levels were not predictive of prostate cancer. CONCLUSIONS: Our findings suggest that serum VEGF-A is not helpful to predict prostate cancer in patients with clinical and/or biologic suspicion of prostate cancer.

Aged↗

Evaluation of the mouse prostate as a suitable model for the study of human prostate function.

INTRODUCTION: Research into prostate development and function is mainly carried out in rats and guinea pigs. While these animals have proven to be good models of human prostate function, their use is limited when compared with what could be achieved using the various currently available gene knockout mice. This study aimed to ascertain whether the mouse prostate was a viable model for studying human prostate function. METHODS: Sections from mouse prostate glands were histochemically processed to visualise the neurotransmitters and receptors present. Isolated organ bath studies were conducted in Krebs-Henseleit solution at 37 degrees C to delineate the physiological mechanisms involved in contractility. RESULTS: Positive histochemical staining for noradrenaline and acetylcholinesterase (AChE) was observed in the fibromuscular stroma. AChE-positive staining was also observed in epithelial cells lining prostatic acini. Immunoreactivity to P2X(1) and P2X(7) purinoceptors was observed in the fibromuscular stroma and immunoreactivity to P2X(4) purinoceptors in the glandular epithelium. Positive immunostaining for neuropeptide Y, big endothelin, calcitonin gene-related peptide (CGRP), substance P, and neurokinin A was observed in the fibromuscular stroma. Frequency-response curves (1.0 ms pulse duration, 60 V, 0.1-20 Hz) to electrical field stimulation yielded frequency-dependent contractions that were attenuated by tetrodotoxin (P < .001), guanethidine (P < .001), and prazosin (P = .01). Suramin (P = .21), alpha,beta-methylene ATP (P = .84), and atropine (P = .76) caused no significant effects. Concentration-response curves to endogenously administered phenylephrine yielded concentration-dependent contractions (pEC(50) = 6.1 +/- 0.3, maximum response 0.20 +/- 0.03 g), which were attenuated by prazosin (P < .001). DISCUSSION: Histochemistry suggests that mouse prostates have a similar innervation to that of humans and other laboratory animals. Furthermore, responses to nerve stimulation are noradrenergic and mediated by alpha(1)-adrenoceptors. Therefore, the mouse prostate is a suitable model for human prostate function and a viable isolated preparation for contractility studies.

Acetylcholinesterase↗

Sons of men with prostate cancer: their attitudes regarding possible inheritance of prostate cancer, screening, and genetic testing.

OBJECTIVES: To study attitudes regarding possible inheritance of prostate cancer among sons of men with prostate cancer. METHODS: A questionnaire was sent to 69 men with prostate cancer and their 101 unaffected sons. All participants were also interviewed by telephone. Sociodemographic data were collected, as were data about the fathers' disease. RESULTS: The response rate was high; 100 sons (99%) and 65 fathers (94%) answered all questions. Sixty of the sons claimed they had worries about having an increased risk of prostate cancer due to possible inheritance. About 90% of the sons wanted to know whether prostate cancer was inheritable (66 definitely and 24 probably), were positively inclined to undergo screening (65 definitely and 27 probably), and to undergo genetic testing (50 definitely and 41 probably), provided there had been multiple cases of prostate cancer in their family. An interest to know whether prostate cancer could be inherited was more frequent among sons with less than 12 years of education, worries about inheritance, younger age, a father treated with curative intent, and with children of their own, especially if sons. Interest in genetic testing was associated with less than 12 years of education and with worries about inheritance. CONCLUSIONS: A large majority of healthy men with a family history of prostate cancer were interested in knowing whether the disease could be inherited and were positively inclined to undergo screening and genetic testing. Our findings indicate that genetic counseling and a screening program could have beneficial psychological effects in families with multiple cases of prostate cancer.

Adult↗

Comparison of prostate size in university and Veterans Affairs Health Care System patients with negative prostate biopsies.

OBJECTIVES: Many important prostate studies take place at Veterans Affairs hospitals. We have examined whether the patient population at these institutions is comparable to the population presenting for prostate evaluation at university hospitals. METHODS: We included all patients presenting for transrectal ultrasound (TRUS) and biopsy in whom systematic biopsies failed to reveal prostate cancer at both Stanford University Medical Center (90 patients) and the Palo Alto Veterans Affairs Health Care System (103 patients) from August 1, 1995 to July 31, 1996. Identical techniques and equipment for TRUS examination and prostate size determination were used at both institutions. RESULTS: There was no significant difference in the age or prostate-specific antigen (PSA) levels of the patients at the two institutions. The mean prostatic volume of the Stanford University patients was 71 cm3 (median 63 cm3), whereas the mean prostatic volume of patients at the Palo Alto Veterans Affairs hospital was 52 cm3 (median 43 cm3), a highly statistically significant difference (P = 0.0009). CONCLUSIONS: The smaller size of the prostate glands in Veterans Affairs patients may be the result of differences in referral base, socioeconomic factors, or environmental factors. These data may have significance for trials conducted only on the prostates of men who are seen at Veterans Affairs hospitals.

Adult↗

Histopathology of the frozen prostate. The microscopic bases of prostatic carcinoma cryoablation.

In the last few years percutaneous cryoablation surgery of the prostate has been re-introduced as an alternative means to treat prostatic carcinoma. Advantages of the technique include local effectiveness in eradicating tumors, minimal morbidity rate and lower costs when compared to radical surgery. We report a study documenting the histopathological changes seen in 317 biopsy specimens obtained from 30 patients (age range 59-83 years, median 73 years) treated with cryosurgical ablation for prostate cancer. Pre- and postoperatory assessment was inclusive of plain clinical, laboratory and instrumental data (digital rectal examination, transrectal ultrasound scan, serum prostatic specific antigen concentration) and systematic biopsies obtained from conventional and modified prostate sextants. Fifteen patients had tumors extending through the prostate capsule (pT3 and pT4). Six patients had stage PT1 tumors and 9 had stage pT2. Tissues were sampled at 3, 6 and between 12-18 months postoperatively. The histologic findings, in decreasing order of frequency, were: full core fibrosis, necrosis, granulation tissue, basal cell hyperplasia, cell swelling, hemosiderin deposits, chronic inflammation, thick nerves and prostatic hyperplasia. Necrosis was of the coagulative type, sometimes associated with nuclear debris, and seen at relatively short interval from cryotherapy. Fibrosis with hyaline qualities was seen especially at 12-18 month interval. The presence of necrosis, as well as granulation tissue, hemosiderin deposits and cell swelling, strongly correlate to intervals from cryosurgical ablation. Residual tumor tissue was focal (0.5-1 mm) and recognizable in 9 cores from 4 patients (13.3%) sampled especially from the prostatic apex. Incipient tumor necrosis was seen in 11 cores, without particular distribution. These findings indicate that cryosurgery results in distinctive changes in both tumoral and non-tumoral prostate tissue. Knowledge of the histopathologic patterns is important since it provides the clinicians with information on treatment efficacy or failure, and could assist in the selection of larger groups of patients eligible to cryosurgical ablation.

Aged↗

CAG repeat length in the androgen receptor gene is related to age at diagnosis of prostate cancer and response to endocrine therapy, but not to prostate cancer risk.

The length of the polymorphic CAG repeat in the N-terminal of the androgen receptor (AR) gene is inversely correlated with the transactivation function of the AR. Some studies have indicated that short CAG repeats are related to higher risk of prostate cancer. We performed a case-control study to investigate relations between CAG repeat length and prostate cancer risk, tumour grade, tumour stage, age at diagnosis and response to endocrine therapy. The study included 190 AR alleles from prostate cancer patients and 186 AR alleles from female control subjects. All were whites from southern Sweden. The frequency distribution of CAG repeat length was strikingly similar for cases and controls, and no significant correlation between CAG repeat length and prostate cancer risk was detected. However, for men with non-hereditary prostate cancer (n = 160), shorter CAG repeats correlated with younger age at diagnosis (P = 0.03). There were also trends toward associations between short CAG repeats and high grade (P = 0.07) and high stage (P = 0.07) disease. Furthermore, we found that patients with long CAG repeats responded better to endocrine therapy, even after adjusting for pretreatment level of prostate-specific antigen and tumour grade and stage (P = 0.05). We conclude that short CAG repeats in the AR gene correlate with young age at diagnosis of prostate cancer, but not with higher risk of the disease. Selection of patients with early onset prostate cancer in case-control studies could therefore lead to an over-estimation of the risk of prostate cancer for men with short CAG repeats. An association between long CAG repeats and good response to endocrine therapy was also found, but the mechanism and clinical relevance are unclear.

Adult↗

Breast and prostate cancer in the relatives of men with prostate cancer.

OBJECTIVE: To assess the risk of breast, ovarian and prostate cancer in the families of men with prostate cancer. PATIENTS AND METHODS: A case-control study was performed by interviewing patients with prostate cancer and obtaining detailed information on family histories of cancer. Controls were hospital-based patients, of a similar age to the cases, with bladder cancer or benign prostatic hypertrophy. RESULTS: A total of 209 cases and 322 controls were interviewed; of the cases, 22.5% had family members with a history of one or more of breast, ovarian or prostate cancers, compared with 15.2% of controls (P < 0.05). The odds ratio (OR) of having prostate cancer when there was a positive family history was 8.22 and the OR of a female relative of a patient with prostate cancer having breast cancer was 1.51. There was no apparent increased risk of ovarian or any other cancer. CONCLUSIONS: We confirm previous reports of an increased incidence of prostate cancer in the families of men with prostate cancer and report a similarly increased incidence of breast cancer in female relatives. We suggest that detailed family histories be taken routinely and intend to analyse blood samples provided from this study for genetic abnormalities.

Age of Onset↗

Hybrid laser treatment compared with transurethral resection of the prostate for symptomatic bladder outlet obstruction caused by a large benign prostate: a prospective, randomized trial with a 6-month follow-up.

OBJECTIVE: To compare the efficacy and safety of hybrid laser treatment, i.e. the combination of visual Nd-YAG laser ablation of prostate and contact Nd-YAG laser vaporization of prostate, with transurethral resection of the prostate (TURP) in the treatment of patients with symptomatic bladder outlet obstruction secondary to a benign high-volume prostate. PATIENTS AND METHODS: Forty-five symptomatic patients with hyperplastic prostates of >40 mL were randomized to undergo either hybrid laser treatment (21) or TURP (24). All patients were evaluated before and after treatment with a complex urodynamic assessment, and were accepted into the study only if they had infravesical obstruction in the pressure-flow study. In the hybrid method, Nd-YAG laser energy was first delivered by an 'adenoma-dependent' approach to all areas of the obstructing lateral lobe tissue through a side-firing gold-alloy tip fibre at 40 W for 90 s of 'burn'. The prostatic urethra was then opened and the median lobe vaporized using the a contact probe at 40 W. Patients were re-evaluated 3 and 6 months after treatment. RESULTS: Both treatments proved to be safe, and improved the subjective and objective outcome measures at 3 and 6 months compared with baseline values. After 3 months, there was a greater improvement in the TURP group in peak urinary flow rate (Qmax; P<0.01), mean urinary flow rate (Qave; P<0.01) and postvoid residual urine volume (P<0.05) than in the hybrid laser group. After 6 months, there was a greater improvement in the TURP group in detrusor pressure at Qmax (P<0.01), Qave (P<0.05) and prostate size (P<0.001) than in the hybrid laser group. In the pressure-flow study at 6 months, a higher proportion of patients (seven of 19) were still obstructed in the hybrid laser group than in TURP group (two of 21; P<0.05). TURP caused more intraoperative blood loss (P<0.001) and postoperative problems associated with bleeding; 38% of hybrid laser patients were discharged with a suprapubic catheter, whereas all TURP patients could urinate at discharge (P<0.01). The duration of bladder drainage was longer after hybrid laser treatment (P<0.001). CONCLUSION: The hybrid laser method was a safe but less effective treatment than TURP for benign prostatic enlargement in patients with prostates of >40 mL.

Aged↗

Correlation between major histocompatibility complex class I molecules and CD8+ T lymphocytes in prostate, and quantification of CD8 and interferon-gamma mRNA in prostate tissue specimens.

OBJECTIVE: To investigate the immunology of host-tumour interaction, critical for the development of immunotherapy against cancers, by assessing the major histocompatibility complex (MHC) class I expression in both benign and malignant prostate disease, and the relationship between their expression and degree of tumour-infiltrating lymphocytes. MATERIALS AND METHODS: Direct serial analysis of gene expression in tumours is an extremely sensitive and powerful tool for monitoring immunological changes in the immunotherapy of solid tumours. Most previous monitoring protocols rely mainly on the analysis of patient's peripheral blood but in the present study the direct molecular analysis of small tissue samples was used, and its accuracy compared with that of conventional immunohistochemical analysis. Twenty-four formalin-fixed, paraffin-embedded prostate samples (11 benign and 13 carcinoma) were used for the immunohistochemical analysis of CD8+ T lymphocytes and MHC class I expression. CD8+ T lymphocytes were counted using an ocular grid and MHC class I measured using digital image-analysis software. Twenty-seven frozen prostate tissue samples (12 benign and 15 carcinoma) were used for direct gene measurements of CD8 and interferon-gamma using a quantitative real-time polymerase chain reaction. RESULTS: There were significantly fewer CD8+ T lymphocytes in prostate carcinoma nests than in benign prostate. There was a significant correlation between the number of CD8+ T lymphocytes and MHC class I expression in the prostate. There was a strong correlation between the immunohistochemical estimates of CD8+ T lymphocytes and CD8 gene by polymerase chain reaction, but no significant difference between benign prostate and prostate carcinoma tissue in gene measurements. CONCLUSION: Down-regulation of MHC class I expression by prostate cancer cells is associated with fewer CD8+ T lymphocytes and hence might be important in cancer growth. In addition, the measurement of gene expression in small tissue samples might be useful for monitoring the efficacy of treatment throughout cancer therapy.

Aged↗

Nephrogenic adenoma of the prostatic urethra: a mimicker of prostate adenocarcinoma.

Nephrogenic adenoma, thought to be a benign metaplastic response of the urothelium to injury, can rarely affect the prostatic urethra. Extension of small tubules of nephrogenic adenoma into the underlying prostatic fibromuscular stroma can lead to the misdiagnosis of prostatic adenocarcinoma in transurethral resection specimens and prostate biopsies. We reviewed 26 cases of nephrogenic adenoma involving the prostatic urethra, seen at The Johns Hopkins Hospital from 1990 to 1998, to evaluate the histologic features, which may better define this lesion. Immunohistochemical results were evaluated for cases where the lesion was present on deeper sections. Histologic patterns included the following: tubules in 96% (25 of 26), structures resembling vessels in 73% (19 of 26), cords and individual cells in 46% (12 of 26), papillary configurations in 19% (5 of 26), and signet ring cell-like tubules in 12% (3 of 26). Other features of nephrogenic adenoma, such as thyroidization, were identified in 38% (10 of 26), and peritubular sheaths were seen in 65% (17 of 26) of cases. Nucleoli were prominent in 54% (14 of 26), and no case had mitoses. In the region of nephrogenic adenoma, urothelium was noted in 69% (18 of 26); in 61% (11 of 18) it showed cuboidal metaplasia and 28% (5 of 18) showed squamous metaplasia. Extension of nephrogenic adenoma into muscle was observed in 77% (20 of 26) of cases, 75% (15 of 20) of which had identifiable urothelium overlying the lesion. Blue-tinged mucinous secretions were observed in 32% (8 of 25) of cases. Inflammation was found in all but one case. Nephrogenic adenomas were diffusely positive for 34betaE12 in 11% (1 of 9) of cases, focally positive in 44% (4 of 9), and negative in 44% (4 of 9). In 100% (9 of 9), cytokeratin 7 stains were positive. Focal prostate specific antigen and PSAP positivity were seen in 36% (4 of 11) and 50% (5 of 10) of nephrogenic adenoma cases, respectively. In conclusion, nephrogenic adenoma of the prostatic urethra can mimic prostate cancer because of: 1) the presence of tubules, cords, and signet ring-like tubules; 2) prominent nucleoli; 3) muscle involvement; 4) blue-tinged mucinous secretions; 5) focal prostate specific antigen and PSAP positivity; and 6) negative staining in some cases for 34betaE12. Features useful in the diagnosis of nephrogenic adenoma include the following: 1) distinctive nephrogenic patterns, such as papillary and "vascular," 2) adjacent urothelium, 3) thyroidization, 4) peritubular sheaths, 5) associated inflammation, and 6) positivity for cytokeratin 7 and, in some cases, 34betaE12.

Adenocarcinoma↗

Total prostate and transition zone volumes, and transition zone index are poorly correlated with objective measures of clinical benign prostatic hyperplasia.

PURPOSE: We determined if total prostate volume, transition zone volume or transition zone index is correlated with the severity of clinical benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 93 men 52 to 85 years old, who were referred to a urology outpatient facility for treatment of clinical BPH, elevated serum prostate specific antigen or abnormal digital rectal examination, underwent measurement of total prostate and transition zone volume at transrectal ultrasonography. All men were requested to undergo uroflowmetry and complete the American Urological Association (AUA) symptom score. RESULTS: The pairwise correlations between AUA symptom score, versus total prostate and transition zone volumes and transition zone index were not statistically or clinically significant. A weak pairwise relationship was observed between peak flow rate versus total prostate volume (r2 = 0.160), transition zone volume (r2 = 0.156) and transition zone index (r2 = 0.147). The pairwise relationships between AUA symptom scores versus all prostate volumes were not statistically significant for subjects with mild (score 8 or less) or moderate to severe (score more than 8) symptoms. CONCLUSIONS: Total prostate and transition zone volumes, and transition zone index are not directly related to AUA symptom score and only weakly related to peak flow rate. These findings provide further evidence that the total prostate, total BPH and relative BPH volumes are not useful determinants of the severity of clinical BPH.

Aged↗

Increased prostatic lysophosphatidylcholine acyltransferase activity in human prostate cancer: a marker for malignancy.

PURPOSE: Phospholipase A2 and lysophosphatidylcholine acyltransferase (LAT) constitute a deacylation-reacylation cycle that incorporates arachidonic acid into the lipid membrane. In a preliminary report we found increased LAT activity in malignant prostate tissue. We measured LAT activity in prostate tissue from a large number of patients undergoing prostatectomy. MATERIALS AND METHODS: Prostate tissue from 93 patients undergoing radical prostatectomy for prostate carcinoma, 14 undergoing cystoprostatectomy for bladder cancer, 55 undergoing transurethral resection for benign prostatic hyperplasia and 11 with prostate cancer undergoing transurethral resection for relief of obstructive symptoms was analyzed for LAT activity. RESULTS: In radical prostatectomy specimens using oleoyl coenzyme A as substrate mean increase in LAT activity between malignant and benign portions of the same specimen was 0.68 +/- 0.12 nmol./mg. protein per minute (p <0.00001). In all radical prostatectomy specimens analyzed LAT activity was 43% higher in the malignant than benign portions (2.25 +/- 0.15 versus 1.57 +/- 0.11 nmol./mg. protein per minute, p <0.001). In the 10 benign prostate specimens obtained from cystoprostatectomy mean LAT activity was 1.12 +/- 0.18 nmol./mg. protein per minute, which was significantly lower than that of benign portions of radical prostatectomy (p <0.05). LAT activity in benign cystoprostatectomy specimens was significantly higher than that in the 50 benign transurethral resection specimens (0.54 +/- 0.05, p <0.01), possibly due to heat damage in transurethral resection specimens during collection. However, LAT activity in transurethral resection specimens from patients with known prostate cancer was similarly increased. Similar results were obtained using arachidonoyl coenzyme A. CONCLUSIONS: We demonstrated increased LAT activity in malignant tissue from patients with prostate cancer. Thus, the deacylation-acylation remodeling cycle may be enhanced to provide more arachidonic acid to meet the demand for prostaglandin E2 synthesis in malignant tissue.

1-Acylglycerophosphocholine O-Acyltransferase↗

The use of rectal balloon during the delivery of intensity modulated radiotherapy (IMRT) for prostate cancer: more than just a prostate gland immobilization device?

PURPOSE: The purpose of this study was to investigate the role of a rectal balloon for prostate immobilization and rectal toxicity reduction in patients receiving dose-escalated intensity-modulated radiotherapy for prostate cancer. PATIENTS AND METHODS: Patients with localized prostate cancer who were undergoing intensity-modulated radiotherapy were treated in a prone position, immobilized with a customized Vac-Lok bag (MED-TEC, Orange City, IA). A rectal balloon with 100 cc of air was used to immobilize the prostate. The prostate displacements were measured using computed tomography (CT)-CT fusion on 10 patients who received radioactive seed implant before intensity-modulated radiotherapy. They were scanned twice weekly during 5 weeks of intensity-modulated radiotherapy, and breathing studies were also performed. Rectal toxicity was evaluated by use of Radiation Therapy Oncology Group scoring in 100 patients. They were treated to a mean dose of 76 Gy over 35 fractions (2.17-Gy fraction size). Dose-volume histogram of the rectum was assessed. A film phantom was constructed to simulate the 4-cm diameter air cavity that was created by the rectal balloon. Kodak XV2 films (Rochester NY) were used to measure and compare dose distribution with and without the air cavity. A fraction of 1.25 Gy was delivered to the phantom at isocenter with 15-MV photons by use of the NOMOS Peacock system and the MIMiC treatment delivery system (Sewickley, PA). RESULTS: The anterior-posterior and lateral prostate displacements were minimal, on the order of measurement uncertainty (approximately 1 mm). The standard deviation of superior-inferior displacement was 1.78 mm. Breathing studies showed no organ displacement during normal breathing when the rectal balloon was in place. The rectal toxicity profile was very favorable: 83% (83/100) patients had no rectal complaint, and 11% and 6% had grade 1 and 2 toxicity, respectively. Dose-volume histogram analysis revealed that in all of the patients, no more than 25% of the rectum received 70 Gy or greater. As visualized by film dosimetry, the dose at air-tissue interface was approximately 15% lower than that without an air cavity. The dose built up rapidly so that at 1 and 2 mm, the differential was approximately 8% and 5%, respectively. The dosimetric coverage at the depth of the posterior prostate wall was essentially equal, with or without the air cavity. DISCUSSION: The use of a rectal balloon during intensity-modulated radiotherapy significantly reduces prostate motion. Prostate immobilization thus allows a safer and smaller planning target volume margin. It has also helped spare the anterior rectal wall (by its dosimetric effects) and reduced the rectal volume that received high-dose radiation (by rectal wall distension). All these factors may have further contributed to the decreased rectal toxicity achieved by intensity-modulated radiotherapy, despite dose escalation and higher-than-conventional fraction size.

Catheterization↗

Transperineal interstitial permanent prostate brachytherapy for Japanese prostate cancer patients in Hawaii.

BACKGROUND: Our aim was to report clinical and biochemical outcomes of transperineal interstitial permanent prostate brachytherapy in the treatment of Japanese patients with clinically organ-confined prostate cancer in Hawaii. METHODS: Ninety-five Japanese patients underwent transperineal interstitial permanent prostate brachytherapy using either iodine-125 or palladium-103 for clinical T1c-T2b N0 M0 prostate cancer. These procedures were carried out between December 1998 and December 2002 at The Queen's Medical Center in Honolulu, Hawaii. Prostate-specific antigen measurements were collected from all patients at follow up. Biochemical failure was defined by three consecutive rises in prostate-specific antigen levels, based on the criteria of the American Society for Therapeutic Radiology and Oncology Consensus panel. RESULTS: The median patient age was 71 years (range, 46-87 years). Thirty-six patients were implanted with either iodine-125 or palladium-103 as monotherapy; 59 patients received moderate-dose external beam irradiation first, followed by a prostate brachytherapy boost. The median follow-up length, calculated from the day of implantation, was 801 days (range, 237-1421 days). During this follow-up period, The Kaplan-Meier estimate of freedom from biochemical failure in this series was 94%. No major complications were observed. CONCLUSIONS: Clinical and biochemical outcomes in the treatment of Japanese patients in Hawaii suffering from localized prostate cancer, using transperineal interstitial permanent prostate brachytherapy, with or without external beam irradiation, compared favorably to results in similarly treated patients in the general US population.

Aged↗

Adrenergic and cholinergic receptors in the human prostate, prostatic capsule and bladder neck.

The adrenergic and cholinergic receptors of the human prostatic capsule, prostatic "adenoma", and bladder neck, were investigated by the in-vitro isometric technique. The prostatic capsule was found to be very rich in both alpha-adrenergic receptors and cholinergic receptors. The prostatic adenoma was moderately rich in alpha-adrenergic receptors, but cholinergic receptors were absent. Beta-adrenergic receptors were absent in the prostatic adenoma, and there was an equivocal response in less than half the specimens of the prostatic capsule. An attempt was made to distinguish between the trigonal component at the posterior bladder neck, and the true bladder neck muscle both posteriorly and antero-laterally. The results indicat that the "posterior bladder neck" seen at operation is predominantly trigonal muscle, and is poor in cholinergic receptors. The adrenergic response is variable in the true bladder neck muscle, but is present and strong in the trigonal muscle. This response is characteristically gradual in its development. In view of the findings in this investigation, it is suggested that certain instances of acute retention of urine in prostatic patients are due to over-stimulation of the alpha-adrenergic receptors, particularly those in the prostatic capsule. Similarly, the accepted clinical contraindication to the use of cholinergic drugs for retention in the prostatic patient is supported by the distribution of the cholinergic receptors in the tissues examined.

Acetylcholine↗